UnbiasedDTI: Mitigating Real-World Bias of Drug-Target Interaction Prediction by Using Deep Ensemble-Balanced Learning

Drug-target interaction (DTI) prediction through in vitro methods is expensive and time-consuming. On the other hand, computational methods can save time and money while enhancing drug discovery efficiency. Most of the computational methods frame DTI prediction as a binary classification task. One important challenge is that the number of negative interactions in all DTI-related datasets is far greater than the number of positive interactions, leading to the class imbalance problem. As a result, a classifier is trained biased towards the majority class (negative class), whereas the minority class (interacting pairs) is of interest. This class imbalance problem is not widely taken into account in DTI prediction studies, and the few previous studies considering balancing in DTI do not focus on the imbalance issue itself. Additionally, they do not benefit from deep learning models and experimental validation. In this study, we propose a computational framework along with experimental validations to predict drug-target interaction using an ensemble of deep learning models to address the class imbalance problem in the DTI domain. The objective of this paper is to mitigate the bias in the prediction of DTI by focusing on the impact of balancing and maintaining other involved parameters at a constant value. Our analysis shows that the proposed model outperforms unbalanced models with the same architecture trained on the BindingDB both computationally and experimentally. These findings demonstrate the significance of balancing, which reduces the bias towards the negative class and leads to better performance. It is important to note that leaning on computational results without experimentally validating them and by relying solely on AUROC and AUPRC metrics is not credible, particularly when the testing set remains unbalanced.     

Synthesis of pyrido[3′,2′:4,5]thieno[2,3-e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-one derivatives

Some new pyrido[3′,2′:4,5]thieno[2,3-e]-[1,2,4]triazolo[4,3-a] pyrimidin-5(4H)-ones were prepared through heterocyclization of ethyl 3-aminothieno[2,3-b]pyridine-2-carboxylate with phenyl or ethyl isothiocyanate followed by nucleophilic displacement with hydrazine, and finally cyclocondensation with orthoesters. Correspondence: Abolghasem Davoodnia, Department of Chemistry, School of Sciences, Islamic Azad University, Mashhad Branch, Mashhad 91735-413, Iran.     

New thermally stable condensation polymers containing central ketal moieties derived from malonaldehydetetramethyl acetal and dihydroxyaromatic compounds

Abstract

A number of new condensation polymers with acetal units in the main chain and having linear and ladder-form structure and high thermal stability were synthesized by solution polycondensation of dihydroxyaromatic compounds with malonaldehydetetramethyl acetal as a reactive protected 1,3-dicarbonyl compound. Optimal conditions for polycondensation were obtained via study of the model compounds. In order to obtain high molecular weight polymers, general investigations on the influence of reaction conditions, such as monomer concentration and reaction temperature were carried out. All polymers were obtained in high yields and moderate inherent viscosity ranging from 0.25 to 0.41?dL/g. The proposed chemical structures of condensation polymers were confirmed by ¹H-NMR, ¹³C-NMR, FTIR spectroscopies, TGA, and DSC. Thermal analysis indicated that these polymers are stable up to 360?°C, and a 10% weight loss (T₁₀) were recorded on the TG curves in the temperature range of 381–411?°C in nitrogen atmosphere, indicating their good thermal stability.     

In vitro and in vivo evaluation of cytotoxicity,antioxidant, antibacterial,antifungal, and cutaneous wound healing properties of gold nanoparticles produced via a green chemistry synthesis using Gundelia tournefortii L. as a capping and reducing agent

The exploitation of various plant materials for the biosynthesis of nanoparticles is considered a green technology because it does not involve any harmful chemicals. The aim of the experiment was chemical characterization and evaluation of cytotoxicity, antioxidant, antibacterial, antifungal, and cutaneous wound healing activities of gold nanoparticles using aqueous extract of Gundelia tournefortii L. leaves (AuNPs@GT). These nanoparticles were characterized by fourier transformed infrared spectroscopy (FT‐IR), field emission scanning electron microscopy (FE‐SEM), energy dispersive X‐ray spectroscopy (EDS), and UV–visible spectroscopy. DPPH free radical scavenging test was done to assess the antioxidant properties, which indicated similar antioxidant potentials for AuNPs@GT and butylated hydroxytoluene. Agar diffusion tests were applied to determine the antibacterial and antifungal characteristics. Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), and Minimum Fungicidal Concentration (MFC) were specified by macro‐broth dilution assay. AuNPs@GT indicated higher antibacterial and antifungal effects than all standard antibiotics (p ≤ 0.01). Also, AuNPs@GT inhibited the growth of all bacteria and fungi and removed them at 2‐4 mg/mL concentrations (p ≤ 0.01). In vivo experiment, after creating the cutaneous wound, the rats were randomly divided into six groups: untreated control, treatment with Eucerin basal ointment, treatment with 3% tetracycline ointment, treatment with 0.2% HAuCl₄ ointment, treatment with 0.2% G. tournefortii ointment, and treatment with 0.2% AuNPs@GT ointment. These groups were treated for 10 days. For histopathological and biochemical analysis of the healing trend, a 3 × 3 cm section was prepared from all dermal thicknesses at day 10. Use of AuNPs@GT ointment in the treatment groups substantially reduced (p ≤ 0.01) the wound area, total cells, neutrophil, and lymphocyte and remarkably raised (p ≤ 0.01) the wound contracture, hydroxyl proline, hexosamine, hexuronic acid, fibrocyte, fibroblast, and fibrocytes/fibroblast rate compared to other groups. The synthesized AuNPs@GT had great cell viability dose‐dependently (Investigating the effect of the plant on HUVEC cell line) and revealed this method was nontoxic. The results showed that the leave aqueous extract of G. tournefortii is very good bioreductant in the synthesis of gold nanoparticles for treatment of bacterial, fungal, and skin diseases.     

Sequential charge separation in two axially linked phenothiazine-aluminum(III) porphyrin-fullerene triads

New supramolecular triads (PTZpy→AlPor-C(60), TPTZpy→AlPor-C(60)), containing aluminum(III) porphyrin (AlPor), fullerene (C(60)), and phenothiazine (phenothiazine = PTZ, 2-methylthiophenothaizine = TPTZ) have been constructed. In these triads the fullerene and phenothiazine units are bound axially to opposite faces of the porphyrin plane via covalent and coordination bonds, respectively. The ground- and excited-state properties of the triads and reference dyads are studied using steady-state and time-resolved spectroscopic techniques. The time-resolved data show that photoexcitation results in charge separation from the excited singlet state of the porphyrin to the C(60) unit, generating (Donor)py→AlPor(?+)-C(60)(?-), Donor = PTZ and TPTZ. A subsequent hole shift from the porphyrin to phenothiazine generates the charge-separated state (Donor)(?+)py→AlPor-C(60)(?-). The lifetime of the charge separation exhibits a modest increase from 39 ns in the absence of the donor to 100 ns in PTZpy→AlPor-C(60) and 83 ns in TPTZpy→AlPor-C(60). These lifetimes are discussed in terms of the electronic coupling between phenothiazine, the porphyrin, and C(60).     

Titanium tetrachloride incorporated crosslinked polystyrene copolymer as an efficient and recyclable polymeric Lewis acid catalyst for the synthesis of Β-amino carbonyl compounds at room temperature

An efficient and eco-friendly procedure for one-pot synthesis of β-amino carbonyl compounds by three-component reaction of aromatic aldehydes, acetophenone, and aromatic amines via a Mannich type reaction using a stable tightly bound complex, titanium tetrachloride incorporated crosslinked polystyrene copolymer (PS/TiCl₄), as a water tolerant, recoverable, and reusable polymeric Lewis acid catalyst in ethanol at room temperature is reported. The complex of the polystyrene and TiCl₄ provides a shelf-stable acidic, water tolerant material, and it is not easily hydrolyzed by water. Our findings thus show a novel and improved modification of the Mannich type reaction in terms of mild reaction conditions, clean reaction profiles, applicability to various substrates using a simple workup procedure which makes this reaction an interesting alternative to previously applied procedures. The recyclability of the catalyst makes this protocol environmentally benign.     

Efficient and Green Synthesis of 1,2-Disubstituted Benzimidazoles and Quinoxalines Using Br⊘nsted Acid Ionic Liquid, [(CH2)4SO3HMIM][HSO4], in Water at Room Temperature

1,2-Disubstituted benzimidazoles and quinoxalines have been synthesized in the presence of Br?nsted acid ionic liquid, [(CH₂)₄SO₃HMIM][HSO₄], in water at ambient temperature.     

Sulfur-Doped Binary Layered Metal Oxides Incorporated on Pomegranate Peel-Derived Activated Carbon for Removal of Heavy Metal Ions

In this study, a novel biomass adsorbent based on activated carbon incorporated with sulfur-based binary metal oxides layered nanoparticles (SML-AC), including sulfur (S₂), manganese (Mn), and tin (Sn) oxide synthesized via the solvothermal method. The newly synthesized SML-AC was studied using FTIR, FESEM, EDX, and BET to determine its functional groups, surface morphology, and elemental composition. Hence, the BET was performed with an appropriate specific surface area for raw AC (356 m²·g⁻¹) and modified AC-SML (195 m²·g⁻¹). To prepare water samples for ICP-OES analysis, the suggested nanocomposite was used as an efficient adsorbent to remove lead (Pb²⁺), cadmium (Cd²⁺), chromium (Cr³⁺), and vanadium (V⁵⁺) from oil-rich regions. As the chemical structure of metal ions is influenced by solution pH, this parameter was considered experimentally, and pH 4, dosage 50 mg, and time 120 min were found to be the best with high capacity for all adsorbates. At different experimental conditions, the AC-SML provided a satisfactory adsorption capacity of 37.03–90.09 mg·g⁻¹ for Cd²⁺, Pb²⁺, Cr^3+, and V⁵⁺ ions. The adsorption experiment was explored, and the method was fitted with the Langmuir model (R² = 0.99) as compared to the Freundlich model (R² = 0.91). The kinetic models and free energy (<0.45 KJ·mol⁻¹) parameters demonstrated that the adsorption rate is limited with pseudo-second order (R² = 0.99) under the physical adsorption mechanism, respectively. Finally, the study demonstrated that the AC-SML nanocomposite is recyclable at least five times in the continuous adsorption–desorption of metal ions.